Prion diseases are fatal neurodegenerative disorders characterized by the accumulation of an abnormal isoform of prion protein in the brain. The development of therapeutic drugs for prion diseases directly relates to therapy for human prion diseases, such as Creutzfeldt-Jakob disease, and will significantly contribute to medical care including community medicine. Such therapeutic drugs for prion diseases can also be used as a BSE prevention medicine for animals including humans and domestic and companion animals.
No effective therapy for prion diseases has been developed and thus there has been a demand for prompt discovery of a new therapeutic drug for prion diseases. A number of compounds have been identified that inhibit prion in prion-infected cells (anti-prion compounds), these compounds are inadequate for use as clinical therapeutic drugs for the following reasons: (1) their anti-prion activity is not sufficient, (2) their molecular structure is unsuitable for optimization, (3) their low blood-brain barrier permeability resulting in low anti-prion effect in vivo, in particular, in the brain, which is the organ mainly affected by prion diseases, and (4) their adverse effects, such as hepatic dysfunction.
The inventor discovered novel anti-prion compounds, including the compounds described in Non-Patent Literature 1, and the compounds with higher activity described in Patent Literature 1. The compounds described in Patent Literature 1 were found to be highly effective for the prevention of onset and progression of prion diseases.
However, conventional anti-prion compounds, including those described in Non-Patent Literature 1 and Patent Literature 1, have poor crystallinity and are unstable in the crystalline form. Due to such lack of high purity or storage stability, these compounds are difficult to be clinically applied as medicaments.